In Ras-mutant cancers, unlike RAF-mutant cancers, it has thus far not been possible to inhibit the MAPK pathway sufficiently using therapeutically safe doses of RAF and MEK inhibitors partly due to the limited therapeutic window offered by these drug targets. One in four of all human cancers contain mutant forms of Ras and Ras is the one of the most frequently mutated oncogenes (see e.g., Pylayeva-Gupta, et al., Nat. Rev. Cancer, 2011, 11(11), 761-774). In particular, K-Ras and N-Ras substitutions are frequently observed in pancreatic (95% K-Ras), colon (47% K-Ras), lung (35% K-Ras) and melanoma (28% N-Ras).